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Clinical Trial Results:
Immunogenicity and Safety of Multiple Formulations of an Intramuscular Inactivated, Split Virion Swine-origin A/H1N1 Influenza Vaccine With and Without Adjuvant in Healthy European Subjects Aged 6 to 35 Months

Summary
EudraCT number	2009-013858-32
Trial protocol	FI
Global end of trial date	05 Jan 2011

Results information
Results version number	v1(current)
This version publication date	16 Feb 2016
First version publication date	29 Jan 2015
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

GPF09

ISRCTN number

US NCT number

NCT00956046

WHO universal trial number (UTN)

U1111-1111-5029

Sponsor organisation name

Sanofi Pasteur SA

Sponsor organisation address

2, avenue Pont Pasteur, Lyon cedex 07, France, F-69367

Public contact

Director, Clinical Development, Sanofi Pasteur SA, 33 4 37 37 58 50, stephanie.pepin@sanofipasteur.com

Scientific contact

Director, Clinical Development, Sanofi Pasteur SA, 33 4 37 37 58 50, stephanie.pepin@sanofipasteur.com

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

12 Apr 2011

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

05 Jan 2011

Was the trial ended prematurely?

Main objective of the trial

• To describe the immune response of each candidate vaccine 21 days after each vaccination by hemagglutination inhibition (HAI) and seroneutralization (SN) testing in all subjects. • To describe the antibody persistence eight months (M8) after the first vaccine administration using HAI method in a subset of subjects who received two half doses of either the 15 μg HA or 3.8 μg HA + AF03 vaccine (amendment 2). • To describe the safety profiles (injection site reactions and systemic events) of each candidate vaccine during the 21 days following each vaccination, and serious adverse events throughout the study in all subjects •To describe the immune response against the A/H1N1 strain using the HAI method 21 days after last vaccination with the 2010-2011 NH seasonal TIV administered 13 months after the first vaccination in a subset of subjects who received two half-doses of either the 15 µg HA or 3.8 µg HA + AF03 A/H1N1 influenza vaccines as primary series (amendment 3).

Protection of trial subjects

Only subjects that met all the study inclusion and none of the exclusion criteria were randomized and vaccinated in the study. Vaccinations were performed by qualified and trained study personnel. Subjects with allergy to any of the vaccine components were not vaccinated. After vaccination, subjects were also kept under clinical observation for 30 minutes to ensure their safety. Appropriate medical equipment was also available on site in case of any immediate allergic reactions.

Background therapy

Not applicable

Evidence for comparator

The non-adjuvanted formulation was chosen based on Sanofi Pasteur experience with seasonal influenza vaccine (Vaxigrip).

Actual start date of recruitment

16 Sep 2009

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Finland: 401

Worldwide total number of subjects

401

EEA total number of subjects

401

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

253

Children (2-11 years)

148

Adolescents (12-17 years)

Adults (18-64 years)

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Study subjects were enrolled from 16 September 2009 to 07 October 2009 in 15 clinical centers in Finland.

Screening details

A total of 401 subjects who met all inclusion criteria and none of the exclusion criteria were enrolled and vaccinated.

Period 1 title

Overall trial (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Not blinded

Blinding implementation details

Not applicable

Are arms mutually exclusive

Yes

1.9 μg HA + ½ AF03; 6-11 months

Arm description

Subjects aged 6-11 months who received the half-dose of the 3.8 μg HA A/H1N1 pandemic influenza vaccine adjuvanted with AF03 (1.9 μg HA + ½ AF03 group) on Day 0 and 21.

Arm type

Experimental

Investigational medicinal product name

Swine A/H1N1 Influenza Vaccine (split virion, inactivated, adjuvanted with AF03)

Investigational medicinal product code

452

Other name

Pharmaceutical forms

Emulsion for injection

Routes of administration

Intramuscular use

Dosage and administration details

0.25 mL dose, intramuscular into the deltoid (subjects ≥1 year of age) or thigh (subjects <1 year of age), two doses 21 days apart.

3.8 μg HA + ½ AF03; 6-11 months

Arm description

Subjects aged 6-11 months who received the half-dose of the 7.5 μg HA A/H1N1 pandemic influenza vaccine adjuvanted with AF03 (3.8 μg HA + ½ AF03 group) on Day 0 and 21.

Arm type

Experimental

Investigational medicinal product name

Swine A/H1N1 Influenza Vaccine (split virion, inactivated, adjuvanted with AF03)

Investigational medicinal product code

452

Other name

Pharmaceutical forms

Emulsion for injection

Routes of administration

Intramuscular use

Dosage and administration details

0.25 mL dose, intramuscular into the deltoid (subjects ≥1 year of age) or thigh (subjects <1 year of age), two doses 21 days apart.

3.8 μg HA + AF03; 6-11 months

Arm description

Subjects aged 6-11 months who received a full dose of the 3.8 μg HA A/H1N1 pandemic influenza vaccine adjuvanted with AF03 (3.8 μg HA + AF03 group) on Day 0 and 21.

Arm type

Experimental

Investigational medicinal product name

Swine A/H1N1 Influenza Vaccine (split virion, inactivated, adjuvanted with AF03)

Investigational medicinal product code

452

Other name

Pharmaceutical forms

Emulsion for injection

Routes of administration

Intramuscular use

Dosage and administration details

0.5 mL dose, intramuscular into the deltoid (subjects ≥1 year of age) or thigh (subjects <1 year of age), two doses 21 days apart.

7.5 μg HA; 6-11 months

Arm description

Subjects aged 6-11 months who received a half-dose of the 7.5 μg HA non-adjuvanted A/H1N1 pandemic influenza vaccine on Day 0 and 21.

Arm type

Active comparator

Investigational medicinal product name

Swine A/H1N1 Influenza Vaccine (split virion, inactivated)

Investigational medicinal product code

448

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

0.25 mL dose, intramuscular into the deltoid (subjects ≥1 year of age) or thigh (subjects <1 year of age), two doses 21 days apart.

1.9 μg HA + ½ AF03; 12-35 months

Arm description

Subjects aged 12-35 months who received the half-dose of the 3.8 μg HA A/H1N1 pandemic influenza vaccine adjuvanted with AF03 (1.9 μg HA + ½ AF03 group) on Day 0 and 21.

Arm type

Experimental

Investigational medicinal product name

Swine A/H1N1 Influenza Vaccine (split virion, inactivated, adjuvanted with AF03)

Investigational medicinal product code

452

Other name

Pharmaceutical forms

Emulsion for injection

Routes of administration

Intramuscular use

Dosage and administration details

0.25 mL dose, intramuscular into the deltoid (subjects ≥1 year of age) or thigh (subjects <1 year of age), two doses 21 days apart.

3.8 μg HA + ½ AF03; 12-35 months

Arm description

Subjects aged 12-35 months who received the half-dose of the 7.5 μg HA A/H1N1 pandemic influenza vaccine adjuvanted with AF03 (3.8 μg HA + ½ AF03 group) on Day 0 and 21.

Arm type

Experimental

Investigational medicinal product name

Swine A/H1N1 Influenza Vaccine (split virion, inactivated, adjuvanted with AF03)

Investigational medicinal product code

452

Other name

Pharmaceutical forms

Emulsion for injection

Routes of administration

Intramuscular use

Dosage and administration details

0.25 mL dose, intramuscular into the deltoid (subjects ≥1 year of age) or thigh (subjects <1 year of age), two doses 21 days apart.

3.8 μg HA + AF03; 12-35 months

Arm description

Subjects aged 12-35 months who received a full dose of the 3.8 μg HA A/H1N1 pandemic influenza vaccine adjuvanted with AF03 (3.8 μg HA + AF03 group) on Day 0 and 21.

Arm type

Experimental

Investigational medicinal product name

Swine A/H1N1 Influenza Vaccine (split virion, inactivated, adjuvanted with AF03)

Investigational medicinal product code

452

Other name

Pharmaceutical forms

Emulsion for injection

Routes of administration

Intramuscular use

Dosage and administration details

0.5 mL dose, intramuscular into the deltoid (subjects ≥1 year of age) or thigh (subjects <1 year of age), two doses 21 days apart.

7.5 μg HA; 12-35 months

Arm description

Subjects aged 12-35 months who received a half-dose of the 7.5 μg HA non-adjuvanted A/H1N1 pandemic influenza vaccine on Day 0 and 21.

Arm type

Active comparator

Investigational medicinal product name

Swine A/H1N1 Influenza Vaccine (split virion, inactivated)

Investigational medicinal product code

448

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

0.25 mL dose, intramuscular into the deltoid (subjects ≥1 year of age) or thigh (subjects <1 year of age), two doses 21 days apart.

Number of subjects in period 1	1.9 μg HA + ½ AF03; 6-11 months	3.8 μg HA + ½ AF03; 6-11 months	3.8 μg HA + AF03; 6-11 months	7.5 μg HA; 6-11 months	1.9 μg HA + ½ AF03; 12-35 months	3.8 μg HA + ½ AF03; 12-35 months	3.8 μg HA + AF03; 12-35 months	7.5 μg HA; 12-35 months
Started	48	50	52	51	48	50	52	50
Completed	46	46	48	50	48	50	51	48
Not completed	2	4	4	1	0	0	1	2
Consent withdrawn by subject	1	1	2	1	-	-	-	1
Adverse event, non-fatal	1	1	-	-	-	-	1	1
Protocol deviation	-	2	2	-	-	-	-	-

Baseline characteristics

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Reporting group title

1.9 μg HA + ½ AF03; 6-11 months

Reporting group description

Subjects aged 6-11 months who received the half-dose of the 3.8 μg HA A/H1N1 pandemic influenza vaccine adjuvanted with AF03 (1.9 μg HA + ½ AF03 group) on Day 0 and 21.

Reporting group title

3.8 μg HA + ½ AF03; 6-11 months

Reporting group description

Subjects aged 6-11 months who received the half-dose of the 7.5 μg HA A/H1N1 pandemic influenza vaccine adjuvanted with AF03 (3.8 μg HA + ½ AF03 group) on Day 0 and 21.

Reporting group title

3.8 μg HA + AF03; 6-11 months

Reporting group description

Subjects aged 6-11 months who received a full dose of the 3.8 μg HA A/H1N1 pandemic influenza vaccine adjuvanted with AF03 (3.8 μg HA + AF03 group) on Day 0 and 21.

Reporting group title

7.5 μg HA; 6-11 months

Reporting group description

Subjects aged 6-11 months who received a half-dose of the 7.5 μg HA non-adjuvanted A/H1N1 pandemic influenza vaccine on Day 0 and 21.

Reporting group title

1.9 μg HA + ½ AF03; 12-35 months

Reporting group description

Subjects aged 12-35 months who received the half-dose of the 3.8 μg HA A/H1N1 pandemic influenza vaccine adjuvanted with AF03 (1.9 μg HA + ½ AF03 group) on Day 0 and 21.

Reporting group title

3.8 μg HA + ½ AF03; 12-35 months

Reporting group description

Subjects aged 12-35 months who received the half-dose of the 7.5 μg HA A/H1N1 pandemic influenza vaccine adjuvanted with AF03 (3.8 μg HA + ½ AF03 group) on Day 0 and 21.

Reporting group title

3.8 μg HA + AF03; 12-35 months

Reporting group description

Subjects aged 12-35 months who received a full dose of the 3.8 μg HA A/H1N1 pandemic influenza vaccine adjuvanted with AF03 (3.8 μg HA + AF03 group) on Day 0 and 21.

Reporting group title

7.5 μg HA; 12-35 months

Reporting group description

Subjects aged 12-35 months who received a half-dose of the 7.5 μg HA non-adjuvanted A/H1N1 pandemic influenza vaccine on Day 0 and 21.

Reporting group values	1.9 μg HA + ½ AF03; 6-11 months	3.8 μg HA + ½ AF03; 6-11 months	3.8 μg HA + AF03; 6-11 months	7.5 μg HA; 6-11 months	1.9 μg HA + ½ AF03; 12-35 months	3.8 μg HA + ½ AF03; 12-35 months	3.8 μg HA + AF03; 12-35 months	7.5 μg HA; 12-35 months	Total
Number of subjects	48	50	52	51	48	50	52	50	401
Age categorical
Units: Subjects
In utero	0	0	0	0	0	0	0	0	0
Preterm newborn infants (gestational age < 37 wks)	0	0	0	0	0	0	0	0	0
Newborns (0-27 days)	0	0	0	0	0	0	0	0	0
Infants and toddlers (28 days-23 months)	48	50	52	51	13	15	14	10	253
Children (2-11 years)	0	0	0	0	35	35	38	40	148
Adolescents (12-17 years)	0	0	0	0	0	0	0	0	0
Adults (18-64 years)	0	0	0	0	0	0	0	0	0
From 65-84 years	0	0	0	0	0	0	0	0	0
85 years and over	0	0	0	0	0	0	0	0	0
Age continuous
Units: months
arithmetic mean (standard deviation)	9.4 ( 1.5 )	9 ( 1.7 )	8.9 ( 1.9 )	9.1 ( 1.4 )	27.3 ( 6.4 )	26.3 ( 6.3 )	27.6 ( 6.4 )	27.1 ( 5.9 )	-
Gender categorical
Units: Subjects
Female	25	27	25	27	22	24	28	21	199
Male	23	23	27	24	26	26	24	29	202
Influenza vaccination 2008/2009
Units: Subjects
Yes	0	0	0	0	24	27	31	26	108
No	44	47	48	50	21	20	20	24	274
Unknown	0	0	0	0	3	3	1	0	7
Not applicable	4	3	4	1	0	0	0	0	12
Influenza vaccination 2007/2008
Units: Subjects
Yes	0	0	0	0	17	18	20	21	76
No	0	1	0	0	21	23	25	22	92
Unknown	0	0	0	0	2	2	0	0	4
Not applicable	48	49	52	51	8	7	7	7	229
Influenza vaccination 2006/2007
Units: Subjects
Yes	0	0	0	0	1	0	0	0	1
No	0	0	0	0	15	15	21	15	66
Uknown	0	0	0	0	1	0	0	0	1
Not applicable	48	50	52	51	31	35	31	35	333
Experience influenza infection during the 2008/2009 season
Units: Subjects
Yes	0	0	0	1	1	1	1	2	6
No	47	50	52	49	44	48	49	46	385
Unknown	1	0	0	1	3	1	2	2	10
Subject in contact with a confirmed and/or probable case of H1N1 within 8 months prior to enrollment
Units: Subjects
Yes	0	2	0	0	0	0	0	0	2
No	48	47	52	51	47	49	52	49	395
Unknown	0	1	0	0	1	1	0	1	4

End points

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Reporting group title

1.9 μg HA + ½ AF03; 6-11 months

Reporting group description

Subjects aged 6-11 months who received the half-dose of the 3.8 μg HA A/H1N1 pandemic influenza vaccine adjuvanted with AF03 (1.9 μg HA + ½ AF03 group) on Day 0 and 21.

Reporting group title

3.8 μg HA + ½ AF03; 6-11 months

Reporting group description

Subjects aged 6-11 months who received the half-dose of the 7.5 μg HA A/H1N1 pandemic influenza vaccine adjuvanted with AF03 (3.8 μg HA + ½ AF03 group) on Day 0 and 21.

Reporting group title

3.8 μg HA + AF03; 6-11 months

Reporting group description

Subjects aged 6-11 months who received a full dose of the 3.8 μg HA A/H1N1 pandemic influenza vaccine adjuvanted with AF03 (3.8 μg HA + AF03 group) on Day 0 and 21.

Reporting group title

7.5 μg HA; 6-11 months

Reporting group description

Subjects aged 6-11 months who received a half-dose of the 7.5 μg HA non-adjuvanted A/H1N1 pandemic influenza vaccine on Day 0 and 21.

Reporting group title

1.9 μg HA + ½ AF03; 12-35 months

Reporting group description

Subjects aged 12-35 months who received the half-dose of the 3.8 μg HA A/H1N1 pandemic influenza vaccine adjuvanted with AF03 (1.9 μg HA + ½ AF03 group) on Day 0 and 21.

Reporting group title

3.8 μg HA + ½ AF03; 12-35 months

Reporting group description

Subjects aged 12-35 months who received the half-dose of the 7.5 μg HA A/H1N1 pandemic influenza vaccine adjuvanted with AF03 (3.8 μg HA + ½ AF03 group) on Day 0 and 21.

Reporting group title

3.8 μg HA + AF03; 12-35 months

Reporting group description

Subjects aged 12-35 months who received a full dose of the 3.8 μg HA A/H1N1 pandemic influenza vaccine adjuvanted with AF03 (3.8 μg HA + AF03 group) on Day 0 and 21.

Reporting group title

7.5 μg HA; 12-35 months

Reporting group description

Subjects aged 12-35 months who received a half-dose of the 7.5 μg HA non-adjuvanted A/H1N1 pandemic influenza vaccine on Day 0 and 21.

Primary: Geometric Mean Titers (GMTs) of Antibody Assayed by HAI Method Against A/California (H1N1) Strain in Subjects Age 6 to 11 Months After Vaccination with Intramuscular Inactivated, Split-virion Swine-origin A/H1N1 Influenza Vaccine With or Without Adjuvant

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End point title

Geometric Mean Titers (GMTs) of Antibody Assayed by HAI Method Against A/California (H1N1) Strain in Subjects Age 6 to 11 Months After Vaccination with Intramuscular Inactivated, Split-virion Swine-origin A/H1N1 Influenza Vaccine With or Without Adjuvant ^[1] ^[2]

End point description

Immunogenicity was evaluated using the hemagglutination inhibition (HAI) method.

End point type

Primary

End point timeframe

Day 0 (pre-vaccination) and Day 21 and Day 42 post-vaccination

Notes
[1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Descriptive analyses were performed based on the study groups and the study vaccine administered for this outcome.
[2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Descriptive analyses were performed based on the age group specified.

End point values	1.9 μg HA + ½ AF03; 6-11 months	3.8 μg HA + ½ AF03; 6-11 months	3.8 μg HA + AF03; 6-11 months	7.5 μg HA; 6-11 months
Number of subjects analysed	48	50	52	51
Units: Titers (1/dil)
geometric mean (confidence interval 95%)
Day 0	5 (5 to 5)	5 (5 to 5)	5 (5 to 5)	5 (5 to 5)
Day 21	200 (154 to 259)	256 (204 to 322)	290 (238 to 354)	18.4 (14.1 to 24)
Day 42	3008 (2474 to 3656)	2500 (2102 to 2974)	3241 (2777 to 3783)	184 (142 to 239)

No statistical analyses for this end point

Primary: Geometric Mean Titers (GMTs) of Antibody Assayed by HAI Method Against A/California (H1N1) Strain in Subjects Age 12-35 Months After Vaccination with Intramuscular Inactivated, Split-virion Swine-origin A/H1N1 Influenza Vaccine With or Without Adjuvant

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End point title

Geometric Mean Titers (GMTs) of Antibody Assayed by HAI Method Against A/California (H1N1) Strain in Subjects Age 12-35 Months After Vaccination with Intramuscular Inactivated, Split-virion Swine-origin A/H1N1 Influenza Vaccine With or Without Adjuvant ^[3] ^[4]

End point description

Immunogenicity was evaluated using the hemagglutination inhibition (HAI) method.

End point type

Primary

End point timeframe

Day 0 (pre-vaccination) and Day 21 and Day 42 post-vaccination

Notes
[3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Descriptive analyses were performed based on the study groups and the study vaccine administered for this outcome.
[4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Descriptive analyses were performed based on the age group specified.

End point values	1.9 μg HA + ½ AF03; 12-35 months	3.8 μg HA + ½ AF03; 12-35 months	3.8 μg HA + AF03; 12-35 months	7.5 μg HA; 12-35 months
Number of subjects analysed	48	50	52	50
Units: Titers (1/dil)
geometric mean (confidence interval 95%)
Day 0	5.04 (4.96 to 5.11)	5.21 (4.79 to 5.67)	5 (5 to 5)	5 (5 to 5)
Day 21	253 (191 to 337)	220 (170 to 285)	409 (334 to 502)	28.3 (19.8 to 40.4)
Day 42	2736 (2221 to 3370)	2524 (2143 to 2973)	3748 (3212 to 4374)	244 (174 to 342)

No statistical analyses for this end point

Primary: Percentage of Subjects Age 6-Months with Antibody Titers ≥ 40 (1/dil) Assayed by HAI Method Against A/California (H1N1) Strain After Vaccination with Intramuscular Inactivated, Split-virion Swine-origin A/H1N1 Influenza Vaccine With or Without Adjuvant

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End point title

Percentage of Subjects Age 6-Months with Antibody Titers ≥ 40 (1/dil) Assayed by HAI Method Against A/California (H1N1) Strain After Vaccination with Intramuscular Inactivated, Split-virion Swine-origin A/H1N1 Influenza Vaccine With or Without Adjuvant ^[5] ^[6]

End point description

Immunogenicity was evaluated using the hemagglutination inhibition (HAI) method.

End point type

Primary

End point timeframe

Day 0 (pre-vaccination) and Day 21 and Day 42 post-vaccination

Notes
[5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Descriptive analyses were performed based on the study groups and the study vaccine administered for this outcome.
[6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Descriptive analyses were performed based on the age group specified.

End point values	1.9 μg HA + ½ AF03; 6-11 months	3.8 μg HA + ½ AF03; 6-11 months	3.8 μg HA + AF03; 6-11 months	7.5 μg HA; 6-11 months
Number of subjects analysed	48	50	52	51
Units: Percentage of subjects
number (not applicable)
Day 0	0	0	0	0
Day 21	95.7	97.9	100	32.7
Day 42	100	100	100	98

No statistical analyses for this end point

Primary: Percentage of Subjects Age 12-35 Months with Antibody Titers ≥40 (1/dil) Assayed by HAI Method Against A/California (H1N1) Strain After Vaccination with Intramuscular Inactivated, Split-virion Swine-origin A/H1N1 Influenza Vaccine With or Without Adjuvant

Top of page

End point title

Percentage of Subjects Age 12-35 Months with Antibody Titers ≥40 (1/dil) Assayed by HAI Method Against A/California (H1N1) Strain After Vaccination with Intramuscular Inactivated, Split-virion Swine-origin A/H1N1 Influenza Vaccine With or Without Adjuvant ^[7] ^[8]

End point description

Immunogenicity was evaluated using the hemagglutination inhibition (HAI) method.

End point type

Primary

End point timeframe

Day 0 (pre-vaccination) and Day 21 and Day 42 post-vaccination

Notes
[7] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Descriptive analyses were performed based on the study groups and the study vaccine administered for this outcome.
[8] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Descriptive analyses were performed based on the age group specified.

End point values	1.9 μg HA + ½ AF03; 12-35 months	3.8 μg HA + ½ AF03; 12-35 months	3.8 μg HA + AF03; 12-35 months	7.5 μg HA; 12-35 months
Number of subjects analysed	48	50	52	50
Units: Percentage of subjects
number (not applicable)
Day 0	0	2	0	0
Day 21	97.8	98	100	34
Day 42	100	100	100	97.9

No statistical analyses for this end point

Primary: Percentage of Subjects Age 6-11 Months Achieving Seroconversion or significant increase in Antibody Assayed by HAI Method Against A/California (H1N1) Strain After Intramuscular Inactivated, Split-virion A/H1N1 Influenza Vaccine With or Without Adjuvant

Top of page

End point title

Percentage of Subjects Age 6-11 Months Achieving Seroconversion or significant increase in Antibody Assayed by HAI Method Against A/California (H1N1) Strain After Intramuscular Inactivated, Split-virion A/H1N1 Influenza Vaccine With or Without Adjuvant ^[9] ^[10]

End point description

Immunogenicity was evaluated using the hemagglutination inhibition (HAI) method. Seroconversion was defined as subjects with pre-vaccination titer <10 (1/dil) on Day 0, post-vaccination titer ≥40 (1/dil) or significant increase for subjects with pre-vaccination titer ≥10 (1/dil), ≥4-fold increase of the titer after vaccination (post/pre).

End point type

Primary

End point timeframe

Day 21 and Day 42 post-vaccination

Notes
[9] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Descriptive analyses were performed based on the study groups and the study vaccine administered for this outcome.
[10] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Descriptive analyses were performed based on the age group specified.

End point values	1.9 μg HA + ½ AF03; 6-11 months	3.8 μg HA + ½ AF03; 6-11 months	3.8 μg HA + AF03; 6-11 months	7.5 μg HA; 6-11 months
Number of subjects analysed	48	50	52	51
Units: Percentage of subjects
number (not applicable)
Day 21	95.7	97.9	100	32.7
Day 42	100	100	100	98

No statistical analyses for this end point

Primary: Percentage of Subjects Age 12-35 Months Achieving Seroconversion or significant increase in Antibody Assayed by HAI Method Against A/California (H1N1) Strain After Intramuscular Inactivated, Split-virion A/H1N1 Influenza Vaccine With or Without Adjuvant

Top of page

End point title

Percentage of Subjects Age 12-35 Months Achieving Seroconversion or significant increase in Antibody Assayed by HAI Method Against A/California (H1N1) Strain After Intramuscular Inactivated, Split-virion A/H1N1 Influenza Vaccine With or Without Adjuvant ^[11] ^[12]

End point description

End point type

Primary

End point timeframe

Day 21 and Day 42 post-vaccination

Notes
[11] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Descriptive analyses were performed based on the study groups and the study vaccine administered for this outcome.
[12] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Descriptive analyses were performed based on the age group specified.

End point values	1.9 μg HA + ½ AF03; 12-35 months	3.8 μg HA + ½ AF03; 12-35 months	3.8 μg HA + AF03; 12-35 months	7.5 μg HA; 12-35 months
Number of subjects analysed	48	50	52	50
Units: Percentage of subjects
number (not applicable)
Day 21	97.8	98	100	34
Day 42	100	100	100	97.9

No statistical analyses for this end point

Primary: Percentage of Subjects Age 6 to 11 Months with Neutralizing Antibody Titers ≥40 (1/dil) Assayed by Seroneutralization Method Against A/California (H1N1) Strain After Intramuscular Inactivated, Split-virion A/H1N1 Influenza Vaccine With or Without Adjuvant

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End point title

Percentage of Subjects Age 6 to 11 Months with Neutralizing Antibody Titers ≥40 (1/dil) Assayed by Seroneutralization Method Against A/California (H1N1) Strain After Intramuscular Inactivated, Split-virion A/H1N1 Influenza Vaccine With or Without Adjuvant ^[13] ^[14]

End point description

Immunogenicity was evaluated using the seroneutralization method.

End point type

Primary

End point timeframe

Day 0 (pre-vaccination) and Day 21 and Day 42 post-vaccination

Notes
[13] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Descriptive analyses were performed based on the study groups and the study vaccine administered for this outcome.
[14] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Descriptive analyses were performed based on the age group specified.

End point values	1.9 μg HA + ½ AF03; 6-11 months	3.8 μg HA + ½ AF03; 6-11 months	3.8 μg HA + AF03; 6-11 months	7.5 μg HA; 6-11 months
Number of subjects analysed	48	50	52	51
Units: Percentage of subjects
number (not applicable)
Day 0	0	0	0	0
Day 21	97.9	100	97.8	69.4
Day 42	100	100	100	100

No statistical analyses for this end point

Primary: Percentage of Subjects Age 12-35 Months with Neutralizing Antibody Titers ≥ 40 (1/dil) Assayed by Seroneutralization Method Against A/California (H1N1) Strain After Intramuscular Inactivated, Split-virion A/H1N1 Influenza Vaccine With or Without Adjuvant

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End point title

Percentage of Subjects Age 12-35 Months with Neutralizing Antibody Titers ≥ 40 (1/dil) Assayed by Seroneutralization Method Against A/California (H1N1) Strain After Intramuscular Inactivated, Split-virion A/H1N1 Influenza Vaccine With or Without Adjuvant ^[15] ^[16]

End point description

Immunogenicity was evaluated using the seroneutralization method.

End point type

Primary

End point timeframe

Day 0 (pre-vaccination) and Day 21 and Day 42 post-vaccination

Notes
[15] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Descriptive analyses were performed based on the study groups and the study vaccine administered for this outcome.
[16] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Descriptive analyses were performed based on the age group specified.

End point values	1.9 μg HA + ½ AF03; 12-35 months	3.8 μg HA + ½ AF03; 12-35 months	3.8 μg HA + AF03; 12-35 months	7.5 μg HA; 12-35 months
Number of subjects analysed	48	50	52	50
Units: Percentage of subjects
number (not applicable)
Day 0	0	0	1.9	0
Day 21	100	98	100	76.6
Day 42	100	100	100	97.9

No statistical analyses for this end point

Primary: Geometric Mean Titers (GMTs) of Neutralizing Antibody Assayed by Seroneutralization Method Against A/California (H1N1) Strain in Subjects Age 6-11 Months After Intramuscular Inactivated, Split-virion A/H1N1 Influenza Vaccine With or Without Adjuvant

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End point title

Geometric Mean Titers (GMTs) of Neutralizing Antibody Assayed by Seroneutralization Method Against A/California (H1N1) Strain in Subjects Age 6-11 Months After Intramuscular Inactivated, Split-virion A/H1N1 Influenza Vaccine With or Without Adjuvant ^[17] ^[18]

End point description

Immunogenicity was evaluated using the seroneutralization method.

End point type

Primary

End point timeframe

Day 0 (pre-vaccination) and Day 21 and Day 42 post-vaccination

Notes
[17] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Descriptive analyses were performed based on the study groups and the study vaccine administered for this outcome.
[18] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Descriptive analyses were performed based on the age group specified.

End point values	1.9 μg HA + ½ AF03; 6-11 months	3.8 μg HA + ½ AF03; 6-11 months	3.8 μg HA + AF03; 6-11 months	7.5 μg HA; 6-11 months
Number of subjects analysed	48	50	52	51
Units: Titers (1/dil)
geometric mean (confidence interval 95%)
Day 0	5.18 (4.82 to 5.57)	5 (5 to 5)	5 (5 to 5)	5 (5 to 5)
Day 21	817 (583 to 1146)	1196 (918 to 1558)	1179 (849 to 1636)	56.4 (39.1 to 81.3)
Day 42	9546 (9085 to 10031)	9214 (8526 to 9956)	9969 (9612 to 10340)	1035 (780 to 1372)

No statistical analyses for this end point

Primary: Geometric Mean Titers (GMTs) of Neutralizing Antibody Assayed by Seroneutralization Method Against A/California (H1N1) Strain in Subjects Age 12-35 Months After Intramuscular Inactivated, Split-virion A/H1N1 Influenza Vaccine With or Without Adjuvant

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End point title

Geometric Mean Titers (GMTs) of Neutralizing Antibody Assayed by Seroneutralization Method Against A/California (H1N1) Strain in Subjects Age 12-35 Months After Intramuscular Inactivated, Split-virion A/H1N1 Influenza Vaccine With or Without Adjuvant ^[19] ^[20]

End point description

Immunogenicity was evaluated using the seroneutralization method.

End point type

Primary

End point timeframe

Day 0 (pre-vaccination) and Day 21 and Day 42 post-vaccination

Notes
[19] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Descriptive analyses were performed based on the study groups and the study vaccine administered for this outcome.
[20] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Descriptive analyses were performed based on the age group specified.

End point values	1.9 μg HA + ½ AF03; 12-35 months	3.8 μg HA + ½ AF03; 12-35 months	3.8 μg HA + AF03; 12-35 months	7.5 μg HA; 12-35 months
Number of subjects analysed	48	50	52	50
Units: Titers (1/dil)
geometric mean (confidence interval 95%)
Day 0	5.09 (4.91 to 5.28)	5 (5 to 5)	5.25 (4.76 to 5.8)	5 (5 to 5)
Day 21	1113 (853 to 1452)	981 (712 to 1351)	1875 (1491 to 2358)	95.1 (59.8 to 151)
Day 42	8539 (7617 to 9571)	9158 (8450 to 9926)	9761 (9185 to 10372)	1170 (791 to 1730)

No statistical analyses for this end point

Primary: Percentage of Subjects Age 6-11 Months with 2- and 4-fold Increase in Neutralizing Antibody Titers Assayed by Seroneutralization Against A/California (H1N1) Strain After Inactivated, Split-virion A/H1N1 Influenza Vaccine With or Without Adjuvant

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End point title

Percentage of Subjects Age 6-11 Months with 2- and 4-fold Increase in Neutralizing Antibody Titers Assayed by Seroneutralization Against A/California (H1N1) Strain After Inactivated, Split-virion A/H1N1 Influenza Vaccine With or Without Adjuvant ^[21] ^[22]

End point description

Immunogenicity was evaluated using the seroneutralization method.

End point type

Primary

End point timeframe

Day 21 and Day 42 post-vaccination

Notes
[21] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Descriptive analyses were performed based on the study groups and the study vaccine administered for this outcome.
[22] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Descriptive analyses were performed based on the age group specified.

End point values	1.9 μg HA + ½ AF03; 6-11 months	3.8 μg HA + ½ AF03; 6-11 months	3.8 μg HA + AF03; 6-11 months	7.5 μg HA; 6-11 months
Number of subjects analysed	48	50	52	51
Units: Percentage of subjects
number (not applicable)
≥2-fold increase from Day 0; Day 21	97.9	100	97.8	89.8
≥2-fold increase from Day 0; Day 42	100	100	100	100
≥4-fold increase from Day 0; Day 21	97.9	100	97.8	77.6
≥4-fold increase from Day 0; Day 42	100	100	100	100

No statistical analyses for this end point

Primary: Percentage of Subjects Age 12-35 Months with 2- and 4-fold Increase in Neutralizing Antibody Titers Assayed by Seroneutralization Against A/California (H1N1) Strain After Inactivated, Split-virion A/H1N1 Influenza Vaccine With or Without Adjuvant

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End point title

Percentage of Subjects Age 12-35 Months with 2- and 4-fold Increase in Neutralizing Antibody Titers Assayed by Seroneutralization Against A/California (H1N1) Strain After Inactivated, Split-virion A/H1N1 Influenza Vaccine With or Without Adjuvant ^[23] ^[24]

End point description

Immunogenicity was evaluated using the seroneutralization method.

End point type

Primary

End point timeframe

Day 21 and Day 42 post-vaccination

Notes
[23] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Descriptive analyses were performed based on the study groups and the study vaccine administered for this outcome.
[24] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Descriptive analyses were performed based on the age group specified.

End point values	1.9 μg HA + ½ AF03; 12-35 months	3.8 μg HA + ½ AF03; 12-35 months	3.8 μg HA + AF03; 12-35 months	7.5 μg HA; 12-35 months
Number of subjects analysed	48	50	52	50
Units: Percentage of subjects
number (not applicable)
≥2-fold increase from Day 0; Day 21	100	98	100	89.4
≥2-fold increase from Day 0; Day 42	100	100	100	100
≥4-fold increase from Day 0; Day 21	100	98	100	85.1
≥4-fold increase from Day 0; Day 42	100	100	100	97.9

No statistical analyses for this end point

Primary: Geometric Mean Titers (GMTs) of Antibody Assayed by SRH Method Against A/California (H1N1) Strain in Subjects Age 6 to 11 Months Old Before and After Vaccination with Inactivated, Split Virion Swine-origin A/H1N1 Influenza Vaccine With or Without Adjuvant

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End point title

Geometric Mean Titers (GMTs) of Antibody Assayed by SRH Method Against A/California (H1N1) Strain in Subjects Age 6 to 11 Months Old Before and After Vaccination with Inactivated, Split Virion Swine-origin A/H1N1 Influenza Vaccine With or Without Adjuvant ^[25] ^[26]

End point description

Immunogenicity was evaluated using Single radial hemolysis (SRH) testing.

End point type

Primary

End point timeframe

Day 0 (pre-vaccination) and Day 21 and Day 42 post-vaccination

Notes
[25] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Descriptive analyses were performed based on the study groups and the study vaccine administered for this outcome.
[26] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Descriptive analyses were performed based on the age group specified.

End point values	1.9 μg HA + ½ AF03; 6-11 months	3.8 μg HA + ½ AF03; 6-11 months	3.8 μg HA + AF03; 6-11 months	7.5 μg HA; 6-11 months
Number of subjects analysed	48	50	52	51
Units: Titers (mm2)
geometric mean (confidence interval 95%)
Day 0	4.53 (4.07 to 5.05)	4.32 (3.95 to 4.72)	4.71 (4.19 to 5.3)	4.67 (4.13 to 5.27)
Day 21	75 (67.9 to 82.8)	77.3 (70.8 to 84.5)	78.6 (72.2 to 85.6)	33.1 (29.6 to 37.1)
Day 42	115 (110 to 121)	111 (106 to 116)	116 (112 to 121)	53.5 (49.1 to 58.2)

No statistical analyses for this end point

Primary: Geometric Mean Titers of Antibody Assayed by SRH Against A/California (H1N1) Strain in Subjects Age 12-35 Months Before and After Vaccination with Intramuscular Inactivated, Split Virion Swine-origin A/H1N1 Influenza Vaccine With or Without Adjuvant

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End point title

Geometric Mean Titers of Antibody Assayed by SRH Against A/California (H1N1) Strain in Subjects Age 12-35 Months Before and After Vaccination with Intramuscular Inactivated, Split Virion Swine-origin A/H1N1 Influenza Vaccine With or Without Adjuvant ^[27] ^[28]

End point description

Immunogenicity was evaluated using Single radial hemolysis (SRH) testing.

End point type

Primary

End point timeframe

Day 0 (pre-vaccination) and Day 21 and Day 42 post-vaccination

Notes
[27] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Descriptive analyses were performed based on the study groups and the study vaccine administered for this outcome.
[28] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Descriptive analyses were performed based on the age group specified.

End point values	1.9 μg HA + ½ AF03; 12-35 months	3.8 μg HA + ½ AF03; 12-35 months	3.8 μg HA + AF03; 12-35 months	7.5 μg HA; 12-35 months
Number of subjects analysed	48	50	52	50
Units: Titers (mm2)
geometric mean (confidence interval 95%)
Day 0	5.23 (4.4 to 6.21)	6.18 (5.13 to 7.44)	6.45 (5.31 to 7.83)	5.35 (4.41 to 6.49)
Day 21	83.9 (77.5 to 90.8)	77.1 (68.6 to 86.7)	96.3 (89.5 to 104)	43.2 (36.4 to 51.3)
Day 42	119 (115 to 124)	112 (107 to 118)	124 (121 to 128)	61 (52.8 to 70.4)

No statistical analyses for this end point

Primary: Percentage of Subjects Age 6 to 11 Months Old With Seroprotection Against A/California (H1N1) Strain Following Vaccination with Intramuscular Inactivated, Split Virion Swine-origin A/H1N1 Influenza Vaccine With or Without Adjuvant

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End point title

Percentage of Subjects Age 6 to 11 Months Old With Seroprotection Against A/California (H1N1) Strain Following Vaccination with Intramuscular Inactivated, Split Virion Swine-origin A/H1N1 Influenza Vaccine With or Without Adjuvant ^[29] ^[30]

End point description

Immunogenicity was evaluated using Single radial hemolysis (SRH) testing. Seroprotection was defined as titers ≥25 mm² on Day 0, Day 21 and Day 42.

End point type

Primary

End point timeframe

Day 0 (pre-vaccination) and Day 21 and Day 42 post-vaccination

Notes
[29] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Descriptive analyses were performed based on the age group specified.
[30] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Descriptive analyses were performed based on the age group specified.

End point values	1.9 μg HA + ½ AF03; 6-11 months	3.8 μg HA + ½ AF03; 6-11 months	3.8 μg HA + AF03; 6-11 months	7.5 μg HA; 6-11 months
Number of subjects analysed	48	50	52	51
Units: Percentage of subjects
number (not applicable)
Day 0	0	0	0	0
Day 21	97.9	97.9	100	77.6
Day 42	100	100	100	100

No statistical analyses for this end point

Primary: Percentage of Subjects Age 12 to 35 Months Old With Seroprotection Against A/California (H1N1) Strain Following Vaccination with Intramuscular Inactivated, Split Virion Swine-origin A/H1N1 Influenza Vaccine With or Without Adjuvant

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End point title

Percentage of Subjects Age 12 to 35 Months Old With Seroprotection Against A/California (H1N1) Strain Following Vaccination with Intramuscular Inactivated, Split Virion Swine-origin A/H1N1 Influenza Vaccine With or Without Adjuvant ^[31] ^[32]

End point description

Immunogenicity was evaluated using Single radial hemolysis (SRH) testing. Seroprotection was defined as titers ≥25 mm² on Day 0, Day 21 and Day 42.

End point type

Primary

End point timeframe

Day 0 (pre-vaccination) and Day 21 and Day 42 post-vaccination

Notes
[31] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Descriptive analyses were performed based on the study groups and the study vaccine administered for this outcome.
[32] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Descriptive analyses were performed based on the age group specified.

End point values	1.9 μg HA + ½ AF03; 12-35 months	3.8 μg HA + ½ AF03; 12-35 months	3.8 μg HA + AF03; 12-35 months	7.5 μg HA; 12-35 months
Number of subjects analysed	48	50	52	50
Units: Percentage of subjects
number (not applicable)
Day 0	2.1	0	5.8	4
Day 21	100	98	100	78.7
Day 42	100	100	100	100

No statistical analyses for this end point

Primary: Percentage of Subjects Age 12 to 35 Months Old Reporting Solicited Injection-site or Systemic Reactions After Any Vaccination with Intramuscular Inactivated, Split Virion Swine-origin A/H1N1 Influenza Vaccine With or Without Adjuvant

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End point title

Percentage of Subjects Age 12 to 35 Months Old Reporting Solicited Injection-site or Systemic Reactions After Any Vaccination with Intramuscular Inactivated, Split Virion Swine-origin A/H1N1 Influenza Vaccine With or Without Adjuvant ^[33] ^[34]

End point description

Solicited inj. site: Tenderness (<24 mths)/Pain (≥24 mths), Erythema, Swelling, Induration and Ecchymosis. Solicited systemic reactions (<24 mths): Fever, Vomiting, Crying abnormal, Drowsiness, Appetite loss, Irritability. Solicited systemic reactions (≥24 mths): Fever, Headache, Malaise, Myalgia, and Shivering. Grade 3 Solicited inj. site reactions: Tenderness–Cries when injected limb is moved or the movement is reduced; Pain–Incapacitating, prevents performance of usual activities; Erythema, Swelling, Induration, and Ecchymosis–≥5 cm. Grade 3 Solicited systemic reactions (<24 mths): Fever–>39.5˚C; Vomiting–≥6 episodes/24 hours or requiring parenteral hydration; Crying abnormal - >3 hours; Drowsiness–Sleeping most of the time or difficult to wake; Appetite loss–Refusing ≥3 feeds/meals or refusing most feeds/meals; Irritability–Inconsolable. Grade 3 Solicited systemic reactions (≥24 mths): Fever–≥39.0˚C; Headache, Malaise, Myalgia, and Shivering–Significant, prevents daily activity.

End point type

Primary

End point timeframe

Day 0 up to Day 7 post-any vaccination

Notes
[33] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Descriptive analyses were performed based on the study groups and the study vaccine administered for this outcome.
[34] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Descriptive analyses were performed based on the age group specified.

End point values	1.9 μg HA + ½ AF03; 12-35 months	3.8 μg HA + ½ AF03; 12-35 months	3.8 μg HA + AF03; 12-35 months	7.5 μg HA; 12-35 months
Number of subjects analysed	48	50	52	50
Units: Percentage of subjects
number (not applicable)
Inj. site Pain/Tenderness	58.3	56	55.8	38.8
Grade 3 Inj. site Pain/Tenderness	0	0	3.8	0
Inj. site Erythema	37.5	32	53.8	24.5
Grade 3 Inj. site Erythema	4.2	6	9.6	0
Inj. site Swelling	14.6	12	23.1	14.3
Grade 3 Inj. site Swelling	4.2	4	5.8	0
Inj. site Induration	20.8	30	19.2	10.2
Grade 3 Inj. site Induration	0	0	1.9	2
Inj. site Ecchymosis	12.5	28	9.6	16.3
Grade 3 Inj. site Ecchymosis	0	0	0	0
Vomiting	7.1	13.3	0	0
Grade 3 Vomiting	0	0	0	0
Crying abnormal	28.6	46.7	53.3	50
Grade 3 Crying abnormal	0	0	6.7	10
Drowsiness	28.6	26.7	40	40
Grade 3 Drowsiness	0	0	0	10
Appetite lost	50	60	73.3	40
Grade 3 Appetite lost	0	0	13.3	10
Irritability	35.7	60	66.7	60
Grade 3 Irritability	0	13.3	6.7	20
Headache	8.8	2.9	5.4	5.1
Grade 3 Headache	0	0	0	0
Malaise	29.4	8.6	10.8	25.6
Grade 3 Malaise	14.7	0	0	2.6
Myalgia	26.5	14.3	24.3	12.8
Grade 3 Myalgia	2.9	0	0	0
Fever; 12 to 23 months	28.6	20	26.7	20
Grade 3 Fever; 12 to 23 months	14.3	0	0	0
Fever; 24 to 35 months	11.8	17.1	21.6	5.1
Grade 3 Fever; 24 to 35 months	2.9	2.9	0	0
Shivering	17.6	2.9	24.3	2.6
Grade 3 Shivering	2.9	0	0	0

No statistical analyses for this end point

Primary: Percentage of Subjects Age 6 to 11 Months Old Reporting Solicited Injection-site or Systemic Reactions After Any Vaccination with Intramuscular Inactivated, Split Virion Swine-origin A/H1N1 Influenza Vaccine With or Without Adjuvant

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End point title

Percentage of Subjects Age 6 to 11 Months Old Reporting Solicited Injection-site or Systemic Reactions After Any Vaccination with Intramuscular Inactivated, Split Virion Swine-origin A/H1N1 Influenza Vaccine With or Without Adjuvant ^[35] ^[36]

End point description

End point type

Primary

End point timeframe

Day 0 up to Day 7 post-any vaccination

Notes
[35] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Descriptive analyses were performed based on the study groups and the study vaccine administered for this outcome.
[36] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Descriptive analyses were performed based on the age group specified.

End point values	1.9 μg HA + ½ AF03; 6-11 months	3.8 μg HA + ½ AF03; 6-11 months	3.8 μg HA + AF03; 6-11 months	7.5 μg HA; 6-11 months
Number of subjects analysed	48	50	52	51
Units: Percentage of subjects
number (not applicable)
Inj. site Tenderness	33.3	24.5	46.2	17.6
Grade 3 Inj. site Tenderness	0	0	0	0
Inj. site Erythema	25	22	50	17.6
Grade 3 Inj. site Erythema	2.1	4	0	0
Inj. site Swelling	12.5	8.2	17.3	3.9
Grade 3 Inj. site Swelling	0	2	0	0
Inj. site Induration	25	24.5	36.5	17.6
Grade 3 Inj. site Induration	0	4.1	1.9	0
Inj. site Ecchymosis	6.3	14.3	13.5	9.8
Grade 3 Inj. site Ecchymosis	0	0	0	0
Fever	35.4	46	42.3	13.7
Grade 3 Fever	2.1	6	3.8	0
Vomiting	33.3	22.4	23.1	13.7
Grade 3 Vomiting	0	0	0	0
Crying abnormal	60.4	53.1	57.7	52.9
Grade 3 Crying abnormal	8.3	4.1	1.9	0
Drowsiness	43.8	28.6	51.9	33.3
Grade 3 Drowsiness	4.2	0	1.9	2
Appetite lost	47.9	42.9	48.1	49
Grade 3 Appetite lost	2.1	2	0	3.9
Irritability	66.7	57.1	69.2	76.5
Grade 3 Irritability	2.1	2	1.9	3.9

No statistical analyses for this end point

Primary: Percentage of Subjects Age 24-35 Months with at Least One Solicited Reaction Listed in the EMA Note for Guidance Within 3 Days After Any and Each Vaccination with Intramuscular Inactivated, Split Virion A/H1N1 Influenza Vaccine With or Without Adjuvant

Top of page

End point title

Percentage of Subjects Age 24-35 Months with at Least One Solicited Reaction Listed in the EMA Note for Guidance Within 3 Days After Any and Each Vaccination with Intramuscular Inactivated, Split Virion A/H1N1 Influenza Vaccine With or Without Adjuvant ^[37] ^[38]

End point description

Solicited injection site reactions: Injection site induration ≥5 cm for at least 4 consecutive days and Injection site ecchymosis. Solicited systemic reactions: Pyrexia (recorded temperature > 38°C) for at least 1 day, Malaise, and Shivering.

End point type

Primary

End point timeframe

Day 0 up to Day 3 post-any and each vaccination

Notes
[37] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Descriptive analyses were performed based on the study groups and the study vaccine administered for this outcome.
[38] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Descriptive analyses were performed based on the age group specified.

End point values	1.9 μg HA + ½ AF03; 12-35 months	3.8 μg HA + ½ AF03; 12-35 months	3.8 μg HA + AF03; 12-35 months	7.5 μg HA; 12-35 months
Number of subjects analysed	34	35	37	40
Units: Percentage of subjects
number (not applicable)
Reaction listed in the EMA recommendations	35.3	40	32.4	38.5
Reaction listed in EMA recommendations;Post-inj. 1	20.6	14.3	21.6	25.6
Reaction listed in EMA recommendations;Post-inj. 2	29.4	28.6	21.6	23.7
Inj. site Induration ≥5 cm for 4 days	0	0	0	0
Inj. site Induration ≥5 cm for 4 days; Post-inj. 1	0	0	0	0
Inj. site Induration ≥5 cm for 4 days; Post-inj. 2	0	0	0	0
Inj. site Ecchymosis	11.8	25.7	10.8	17.9
Inj. site Ecchymosis; Post-inj. 1	5.9	11.4	5.4	12.8
Inj. site Ecchymosis; Post-inj. 2	5.9	17.1	5.4	10.5
Pyrexia (temp. > 38°C) for 1 day	11.8	8.6	10.8	2.6
Pyrexia (temp. > 38°C) for 1 day; Post-inj. 1	0	2.9	2.7	2.6
Pyrexia (temp. > 38°C) for 1 day; Post-inj. 2	11.8	5.7	8.1	0
Malaise	29.4	5.7	8.1	20.5
Malaise; Post-inj. 1	17.6	0	5.6	7.7
Malaise; Post-inj. 2	17.6	5.7	8.1	13.2
Shivering	17.6	0	21.6	2.6
Shivering; Post-inj. 1	5.9	0	16.7	2.6
Shivering; Post-inj. 2	17.6	0	10.8	2.6

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Adverse event data were collected from Day 0 (post-vaccination) up to Day 21 post-vaccination.

Assessment type

Non-systematic

Dictionary name

MedDRA

Dictionary version

12.0

Reporting group title

1.9 μg HA + ½ AF03; 6-11 months

Reporting group description

Subjects aged 6-11 months who received the half-dose of the 3.8 μg HA A/H1N1 pandemic influenza vaccine adjuvanted with AF03 (1.9 μg HA + ½ AF03 group) on Day 0 and 21.

Reporting group title

3.8 μg HA + ½ AF03; 6-11 months

Reporting group description

Subjects aged 6-11 months who received the half-dose of the 7.5 μg HA A/H1N1 pandemic influenza vaccine adjuvanted with AF03 (3.8 μg HA + ½ AF03 group) on Day 0 and 21.

Reporting group title

3.8 μg HA + AF03; 6-11 months

Reporting group description

Subjects aged 6-11 months who received a full dose of the 3.8 μg HA A/H1N1 pandemic influenza vaccine adjuvanted with AF03 (3.8 μg HA + AF03 group) on Day 0 and 21.

Reporting group title

7.5 μg HA; 6-11 months

Reporting group description

Subjects aged 6-11 months who received a half-dose of the 7.5 μg HA non-adjuvanted A/H1N1 pandemic influenza vaccine on Day 0 and 21.

Reporting group title

1.9 μg HA + ½ AF03; 12-35 months

Reporting group description

Subjects aged 12-35 months who received the half-dose of the 3.8 μg HA A/H1N1 pandemic influenza vaccine adjuvanted with AF03 (1.9 μg HA + ½ AF03 group) on Day 0 and 21.

Reporting group title

3.8 μg HA + ½ AF03; 12-35 months

Reporting group description

Subjects aged 12-35 months who received the half-dose of the 7.5 μg HA A/H1N1 pandemic influenza vaccine adjuvanted with AF03 (3.8 μg HA + ½ AF03 group) on Day 0 and 21.

Reporting group title

3.8 μg HA + AF03; 12-35 months

Reporting group description

Subjects aged 12-35 months who received a full dose of the 3.8 μg HA A/H1N1 pandemic influenza vaccine adjuvanted with AF03 (3.8 μg HA + AF03 group) on Day 0 and 21.

Reporting group title

7.5 μg HA; 12-35 months

Reporting group description

Subjects aged 12-35 months who received a half-dose of the 7.5 μg HA non-adjuvanted A/H1N1 pandemic influenza vaccine on Day 0 and 21.

Serious adverse events	1.9 μg HA + ½ AF03; 6-11 months	3.8 μg HA + ½ AF03; 6-11 months	3.8 μg HA + AF03; 6-11 months	7.5 μg HA; 6-11 months	1.9 μg HA + ½ AF03; 12-35 months	3.8 μg HA + ½ AF03; 12-35 months	3.8 μg HA + AF03; 12-35 months	7.5 μg HA; 12-35 months
Total subjects affected by serious adverse events
subjects affected / exposed	3 / 48 (6.25%)	4 / 50 (8.00%)	3 / 52 (5.77%)	3 / 51 (5.88%)	1 / 48 (2.08%)	1 / 50 (2.00%)	1 / 52 (1.92%)	2 / 50 (4.00%)
number of deaths (all causes)	0	0	0	0	0	0	0	0
number of deaths resulting from adverse events	0	0	0	0	0	0	0	0
Injury, poisoning and procedural complications
Traumatic brain injury
subjects affected / exposed	0 / 48 (0.00%)	0 / 50 (0.00%)	1 / 52 (1.92%)	0 / 51 (0.00%)	0 / 48 (0.00%)	0 / 50 (0.00%)	0 / 52 (0.00%)	0 / 50 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Congenital, familial and genetic disorders
Duchenne muscular dystrophy
subjects affected / exposed	0 / 48 (0.00%)	0 / 50 (0.00%)	0 / 52 (0.00%)	0 / 51 (0.00%)	0 / 48 (0.00%)	0 / 50 (0.00%)	1 / 52 (1.92%)	0 / 50 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Nervous system disorders
Febrile convulsion
subjects affected / exposed	1 / 48 (2.08%)	0 / 50 (0.00%)	0 / 52 (0.00%)	0 / 51 (0.00%)	1 / 48 (2.08%)	1 / 50 (2.00%)	0 / 52 (0.00%)	1 / 50 (2.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 0	0 / 1	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hepatobiliary disorders
Jaundice
subjects affected / exposed	1 / 48 (2.08%)	0 / 50 (0.00%)	0 / 52 (0.00%)	0 / 51 (0.00%)	0 / 48 (0.00%)	0 / 50 (0.00%)	0 / 52 (0.00%)	0 / 50 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Bronchitis
subjects affected / exposed	1 / 48 (2.08%)	1 / 50 (2.00%)	1 / 52 (1.92%)	1 / 51 (1.96%)	0 / 48 (0.00%)	0 / 50 (0.00%)	0 / 52 (0.00%)	0 / 50 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 1	0 / 2	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastroenteritis rotavirus
subjects affected / exposed	0 / 48 (0.00%)	0 / 50 (0.00%)	1 / 52 (1.92%)	0 / 51 (0.00%)	0 / 48 (0.00%)	0 / 50 (0.00%)	0 / 52 (0.00%)	0 / 50 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Oral herpes
subjects affected / exposed	0 / 48 (0.00%)	1 / 50 (2.00%)	0 / 52 (0.00%)	0 / 51 (0.00%)	0 / 48 (0.00%)	0 / 50 (0.00%)	0 / 52 (0.00%)	0 / 50 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia
subjects affected / exposed	1 / 48 (2.08%)	1 / 50 (2.00%)	0 / 52 (0.00%)	1 / 51 (1.96%)	0 / 48 (0.00%)	0 / 50 (0.00%)	0 / 52 (0.00%)	1 / 50 (2.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory syncytial virus bronchitis
subjects affected / exposed	0 / 48 (0.00%)	0 / 50 (0.00%)	0 / 52 (0.00%)	1 / 51 (1.96%)	0 / 48 (0.00%)	0 / 50 (0.00%)	0 / 52 (0.00%)	0 / 50 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Sepsis
subjects affected / exposed	0 / 48 (0.00%)	1 / 50 (2.00%)	0 / 52 (0.00%)	0 / 51 (0.00%)	0 / 48 (0.00%)	0 / 50 (0.00%)	0 / 52 (0.00%)	0 / 50 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	1.9 μg HA + ½ AF03; 6-11 months	3.8 μg HA + ½ AF03; 6-11 months	3.8 μg HA + AF03; 6-11 months	7.5 μg HA; 6-11 months	1.9 μg HA + ½ AF03; 12-35 months	3.8 μg HA + ½ AF03; 12-35 months	3.8 μg HA + AF03; 12-35 months	7.5 μg HA; 12-35 months
Total subjects affected by non serious adverse events
subjects affected / exposed	32 / 48 (66.67%)	28 / 50 (56.00%)	36 / 52 (69.23%)	39 / 51 (76.47%)	28 / 48 (58.33%)	28 / 50 (56.00%)	29 / 52 (55.77%)	19 / 50 (38.00%)
Nervous system disorders
Drowsiness
alternative assessment type: Systematic
subjects affected / exposed ^[1]	21 / 48 (43.75%)	14 / 49 (28.57%)	27 / 52 (51.92%)	17 / 51 (33.33%)	4 / 14 (28.57%)	4 / 15 (26.67%)	6 / 15 (40.00%)	4 / 10 (40.00%)
occurrences all number	25	23	35	20	6	5	9	4
Headache
alternative assessment type: Systematic
subjects affected / exposed ^[2]	0 / 48 (0.00%)	0 / 50 (0.00%)	0 / 52 (0.00%)	0 / 51 (0.00%)	3 / 34 (8.82%)	1 / 35 (2.86%)	2 / 37 (5.41%)	2 / 39 (5.13%)
occurrences all number	0	0	0	0	3	1	2	3
General disorders and administration site conditions
Pyrexia
subjects affected / exposed	2 / 48 (4.17%)	4 / 50 (8.00%)	1 / 52 (1.92%)	5 / 51 (9.80%)	0 / 48 (0.00%)	0 / 50 (0.00%)	0 / 52 (0.00%)	0 / 50 (0.00%)
occurrences all number	3	5	2	5	0	0	0	0
Injection site tenderness
alternative assessment type: Systematic
subjects affected / exposed ^[3]	16 / 48 (33.33%)	12 / 49 (24.49%)	24 / 52 (46.15%)	9 / 51 (17.65%)	0 / 48 (0.00%)	0 / 50 (0.00%)	0 / 52 (0.00%)	0 / 50 (0.00%)
occurrences all number	22	16	32	12	0	0	0	0
Injection site erythema
alternative assessment type: Systematic
subjects affected / exposed ^[4]	12 / 48 (25.00%)	11 / 50 (22.00%)	26 / 52 (50.00%)	9 / 51 (17.65%)	18 / 48 (37.50%)	16 / 50 (32.00%)	28 / 52 (53.85%)	12 / 49 (24.49%)
occurrences all number	14	14	29	12	23	19	36	14
Injection site swelling
alternative assessment type: Systematic
subjects affected / exposed ^[5]	6 / 48 (12.50%)	4 / 49 (8.16%)	9 / 52 (17.31%)	2 / 51 (3.92%)	7 / 48 (14.58%)	6 / 50 (12.00%)	12 / 52 (23.08%)	7 / 49 (14.29%)
occurrences all number	7	4	9	2	7	6	15	7
Injection site ecchymosis
alternative assessment type: Systematic
subjects affected / exposed ^[6]	3 / 48 (6.25%)	7 / 49 (14.29%)	7 / 52 (13.46%)	5 / 51 (9.80%)	6 / 48 (12.50%)	14 / 50 (28.00%)	5 / 52 (9.62%)	8 / 49 (16.33%)
occurrences all number	3	8	7	5	6	16	5	10
Fever
alternative assessment type: Systematic
subjects affected / exposed ^[7]	17 / 48 (35.42%)	23 / 50 (46.00%)	22 / 52 (42.31%)	7 / 51 (13.73%)	4 / 14 (28.57%)	3 / 15 (20.00%)	4 / 15 (26.67%)	2 / 10 (20.00%)
occurrences all number	19	26	26	9	5	3	6	2
Malaise
alternative assessment type: Systematic
subjects affected / exposed ^[8]	0 / 48 (0.00%)	0 / 50 (0.00%)	0 / 52 (0.00%)	0 / 51 (0.00%)	10 / 34 (29.41%)	3 / 35 (8.57%)	4 / 37 (10.81%)	10 / 39 (25.64%)
occurrences all number	0	0	0	0	12	3	6	12
Shivering
alternative assessment type: Systematic
subjects affected / exposed ^[9]	0 / 48 (0.00%)	0 / 50 (0.00%)	0 / 52 (0.00%)	0 / 51 (0.00%)	6 / 34 (17.65%)	1 / 35 (2.86%)	9 / 37 (24.32%)	1 / 39 (2.56%)
occurrences all number	0	0	0	0	8	1	11	2
Gastrointestinal disorders
Diarrhoea
subjects affected / exposed	4 / 48 (8.33%)	4 / 50 (8.00%)	7 / 52 (13.46%)	3 / 51 (5.88%)	2 / 48 (4.17%)	3 / 50 (6.00%)	0 / 52 (0.00%)	1 / 50 (2.00%)
occurrences all number	5	6	10	3	2	3	0	1
Teething
subjects affected / exposed	8 / 48 (16.67%)	14 / 50 (28.00%)	8 / 52 (15.38%)	15 / 51 (29.41%)	0 / 48 (0.00%)	0 / 50 (0.00%)	0 / 52 (0.00%)	0 / 50 (0.00%)
occurrences all number	12	19	8	19	0	0	0	0
Vomiting
alternative assessment type: Systematic
subjects affected / exposed ^[10]	16 / 48 (33.33%)	11 / 49 (22.45%)	12 / 52 (23.08%)	7 / 51 (13.73%)	1 / 14 (7.14%)	2 / 15 (13.33%)	0 / 15 (0.00%)	0 / 10 (0.00%)
occurrences all number	23	13	13	7	1	2	0	0
Respiratory, thoracic and mediastinal disorders
Cough
subjects affected / exposed	2 / 48 (4.17%)	2 / 50 (4.00%)	3 / 52 (5.77%)	5 / 51 (9.80%)	3 / 48 (6.25%)	5 / 50 (10.00%)	4 / 52 (7.69%)	2 / 50 (4.00%)
occurrences all number	2	2	3	5	3	5	4	2
Skin and subcutaneous tissue disorders
Rash
subjects affected / exposed	0 / 48 (0.00%)	0 / 50 (0.00%)	0 / 52 (0.00%)	0 / 51 (0.00%)	3 / 48 (6.25%)	2 / 50 (4.00%)	0 / 52 (0.00%)	2 / 50 (4.00%)
occurrences all number	0	0	0	0	3	2	0	2
Injection site induration
alternative assessment type: Systematic
subjects affected / exposed ^[11]	12 / 48 (25.00%)	12 / 49 (24.49%)	19 / 52 (36.54%)	9 / 51 (17.65%)	10 / 48 (20.83%)	15 / 50 (30.00%)	10 / 52 (19.23%)	5 / 49 (10.20%)
occurrences all number	14	15	20	10	12	18	13	7
Psychiatric disorders
Crying abnormal
alternative assessment type: Systematic
subjects affected / exposed ^[12]	29 / 48 (60.42%)	26 / 49 (53.06%)	30 / 52 (57.69%)	27 / 51 (52.94%)	4 / 14 (28.57%)	7 / 15 (46.67%)	8 / 15 (53.33%)	5 / 10 (50.00%)
occurrences all number	36	37	35	38	4	9	11	5
Irritability
alternative assessment type: Systematic
subjects affected / exposed ^[13]	32 / 48 (66.67%)	28 / 49 (57.14%)	36 / 52 (69.23%)	39 / 51 (76.47%)	5 / 14 (35.71%)	9 / 15 (60.00%)	10 / 15 (66.67%)	6 / 10 (60.00%)
occurrences all number	45	41	48	57	8	14	15	8
Musculoskeletal and connective tissue disorders
Myalgia
alternative assessment type: Systematic
subjects affected / exposed ^[14]	0 / 48 (0.00%)	0 / 50 (0.00%)	0 / 52 (0.00%)	0 / 51 (0.00%)	9 / 34 (26.47%)	5 / 35 (14.29%)	9 / 37 (24.32%)	5 / 39 (12.82%)
occurrences all number	0	0	0	0	10	6	13	7
Infections and infestations
Ear infection
subjects affected / exposed	4 / 48 (8.33%)	3 / 50 (6.00%)	1 / 52 (1.92%)	2 / 51 (3.92%)	0 / 48 (0.00%)	0 / 50 (0.00%)	0 / 52 (0.00%)	0 / 50 (0.00%)
occurrences all number	4	3	1	2	0	0	0	0
Gastroenteritis
subjects affected / exposed	2 / 48 (4.17%)	3 / 50 (6.00%)	1 / 52 (1.92%)	3 / 51 (5.88%)	0 / 48 (0.00%)	0 / 50 (0.00%)	0 / 52 (0.00%)	0 / 50 (0.00%)
occurrences all number	2	3	1	3	0	0	0	0
Nasopharyngitis
subjects affected / exposed	11 / 48 (22.92%)	6 / 50 (12.00%)	3 / 52 (5.77%)	5 / 51 (9.80%)	3 / 48 (6.25%)	7 / 50 (14.00%)	3 / 52 (5.77%)	6 / 50 (12.00%)
occurrences all number	13	6	3	5	3	7	3	6
Otitis media
subjects affected / exposed	10 / 48 (20.83%)	5 / 50 (10.00%)	5 / 52 (9.62%)	7 / 51 (13.73%)	0 / 48 (0.00%)	0 / 50 (0.00%)	0 / 52 (0.00%)	0 / 50 (0.00%)
occurrences all number	10	6	5	7	0	0	0	0
Respiratory tract infection
subjects affected / exposed	0 / 48 (0.00%)	0 / 50 (0.00%)	0 / 52 (0.00%)	0 / 51 (0.00%)	1 / 48 (2.08%)	1 / 50 (2.00%)	3 / 52 (5.77%)	1 / 50 (2.00%)
occurrences all number	0	0	0	0	1	1	3	1
Rhinitis
subjects affected / exposed	9 / 48 (18.75%)	10 / 50 (20.00%)	12 / 52 (23.08%)	9 / 51 (17.65%)	6 / 48 (12.50%)	9 / 50 (18.00%)	5 / 52 (9.62%)	6 / 50 (12.00%)
occurrences all number	10	11	14	10	7	12	5	6
Upper respiratory tract infection
subjects affected / exposed	7 / 48 (14.58%)	7 / 50 (14.00%)	10 / 52 (19.23%)	11 / 51 (21.57%)	6 / 48 (12.50%)	4 / 50 (8.00%)	7 / 52 (13.46%)	3 / 50 (6.00%)
occurrences all number	8	7	14	11	6	4	7	3
Metabolism and nutrition disorders
Appetite lost
alternative assessment type: Systematic
subjects affected / exposed ^[15]	23 / 48 (47.92%)	21 / 49 (42.86%)	25 / 52 (48.08%)	25 / 51 (49.02%)	7 / 14 (50.00%)	9 / 15 (60.00%)	11 / 15 (73.33%)	4 / 10 (40.00%)
occurrences all number	30	28	30	30	9	12	16	5

Notes
[1] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: This was a solicited adverse event recorded in a diary card within 7 {or 3 as applicable} days of vaccination; the total number (N) reflects those subjects for which the diary cards were returned and for which data were available for the event during the period.
[2] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: This was a solicited adverse event recorded in a diary card within 7 {or 3 as applicable} days of vaccination; the total number (N) reflects those subjects for which the diary cards were returned and for which data were available for the event during the period.
[3] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: This was a solicited adverse event recorded in a diary card within 7 {or 3 as applicable} days of vaccination; the total number (N) reflects those subjects for which the diary cards were returned and for which data were available for the event during the period.
[4] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: This was a solicited adverse event recorded in a diary card within 7 {or 3 as applicable} days of vaccination; the total number (N) reflects those subjects for which the diary cards were returned and for which data were available for the event during the period.
[5] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: This was a solicited adverse event recorded in a diary card within 7 {or 3 as applicable} days of vaccination; the total number (N) reflects those subjects for which the diary cards were returned and for which data were available for the event during the period.
[6] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: This was a solicited adverse event recorded in a diary card within 7 {or 3 as applicable} days of vaccination; the total number (N) reflects those subjects for which the diary cards were returned and for which data were available for the event during the period.
[7] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: This was a solicited adverse event recorded in a diary card within 7 {or 3 as applicable} days of vaccination; the total number (N) reflects those subjects for which the diary cards were returned and for which data were available for the event during the period.
[8] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: This was a solicited adverse event recorded in a diary card within 7 {or 3 as applicable} days of vaccination; the total number (N) reflects those subjects for which the diary cards were returned and for which data were available for the event during the period.
[9] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: This was a solicited adverse event recorded in a diary card within 7 {or 3 as applicable} days of vaccination; the total number (N) reflects those subjects for which the diary cards were returned and for which data were available for the event during the period.
[10] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: This was a solicited adverse event recorded in a diary card within 7 {or 3 as applicable} days of vaccination; the total number (N) reflects those subjects for which the diary cards were returned and for which data were available for the event during the period.
[11] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: This was a solicited adverse event recorded in a diary card within 7 {or 3 as applicable} days of vaccination; the total number (N) reflects those subjects for which the diary cards were returned and for which data were available for the event during the period.
[12] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: This was a solicited adverse event recorded in a diary card within 7 {or 3 as applicable} days of vaccination; the total number (N) reflects those subjects for which the diary cards were returned and for which data were available for the event during the period.
[13] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: This was a solicited adverse event recorded in a diary card within 7 {or 3 as applicable} days of vaccination; the total number (N) reflects those subjects for which the diary cards were returned and for which data were available for the event during the period.
[14] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: This was a solicited adverse event recorded in a diary card within 7 {or 3 as applicable} days of vaccination; the total number (N) reflects those subjects for which the diary cards were returned and for which data were available for the event during the period.
[15] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: This was a solicited adverse event recorded in a diary card within 7 {or 3 as applicable} days of vaccination; the total number (N) reflects those subjects for which the diary cards were returned and for which data were available for the event during the period.

More information

Top of page

Were there any global substantial amendments to the protocol? Yes

09 Sep 2009

The modalities of physical examination to be performed by investigators were changed.

01 Feb 2010

Documented the persistence of anti-HA antibodies in a subset of subjects who received two half-doses of either the 15 μg HA or 3.8 μg HA + AF03 vaccine (i.e. 7.5 μg HA and 1.9 μg HA + ½ AF03 doses, respectively). The subjects included in the antibody persistence evaluation were followed for persistence of the immune response 8 months after the first A/H1N1 vaccination. One more visit (V05) was planned 8 months after the first vaccination to perform blood sampling for the subjects who participated in antibody persistence evaluation.

30 Jun 2010

Evaluated the safety and the immune response to the seasonal trivalent seasonal influenza vaccine 2010-2011 NH formulation on the subjects previously vaccinated with two half-doses of the 3.8 μg HA + AF03 or the unadjuvanted 15 μg HA pandemic influenza vaccines. For subjects aged more than 36 months, two visits, Visit 06, planned one year after the first A/H1N1 pandemic influenza vaccine injection and Visit 07, planned 21 days after Visit 06, were added. For subjects aged less than 36 months, three visits, Visit 06, planned one year after the first A/H1N1 pandemic influenza vaccine injection, Visit 07, planned 21 to 28 days after Visit 06 and Visit 08 planned 42 to 45 days after Visit 6 were added.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

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Clinical trials

Clinical Trial Results: Immunogenicity and Safety of Multiple Formulations of an Intramuscular Inactivated, Split Virion Swine-origin A/H1N1 Influenza Vaccine With and Without Adjuvant in Healthy European Subjects Aged 6 to 35 Months

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Geometric Mean Titers (GMTs) of Antibody Assayed by HAI Method Against A/California (H1N1) Strain in Subjects Age 6 to 11 Months After Vaccination with Intramuscular Inactivated, Split-virion Swine-origin A/H1N1 Influenza Vaccine With or Without Adjuvant

Primary: Geometric Mean Titers (GMTs) of Antibody Assayed by HAI Method Against A/California (H1N1) Strain in Subjects Age 6 to 11 Months After Vaccination with Intramuscular Inactivated, Split-virion Swine-origin A/H1N1 Influenza Vaccine With or Without Adjuvant

Primary: Geometric Mean Titers (GMTs) of Antibody Assayed by HAI Method Against A/California (H1N1) Strain in Subjects Age 12-35 Months After Vaccination with Intramuscular Inactivated, Split-virion Swine-origin A/H1N1 Influenza Vaccine With or Without Adjuvant

Primary: Geometric Mean Titers (GMTs) of Antibody Assayed by HAI Method Against A/California (H1N1) Strain in Subjects Age 12-35 Months After Vaccination with Intramuscular Inactivated, Split-virion Swine-origin A/H1N1 Influenza Vaccine With or Without Adjuvant

Primary: Percentage of Subjects Age 6-Months with Antibody Titers ≥ 40 (1/dil) Assayed by HAI Method Against A/California (H1N1) Strain After Vaccination with Intramuscular Inactivated, Split-virion Swine-origin A/H1N1 Influenza Vaccine With or Without Adjuvant

Primary: Percentage of Subjects Age 6-Months with Antibody Titers ≥ 40 (1/dil) Assayed by HAI Method Against A/California (H1N1) Strain After Vaccination with Intramuscular Inactivated, Split-virion Swine-origin A/H1N1 Influenza Vaccine With or Without Adjuvant

Primary: Percentage of Subjects Age 12-35 Months with Antibody Titers ≥40 (1/dil) Assayed by HAI Method Against A/California (H1N1) Strain After Vaccination with Intramuscular Inactivated, Split-virion Swine-origin A/H1N1 Influenza Vaccine With or Without Adjuvant

Primary: Percentage of Subjects Age 12-35 Months with Antibody Titers ≥40 (1/dil) Assayed by HAI Method Against A/California (H1N1) Strain After Vaccination with Intramuscular Inactivated, Split-virion Swine-origin A/H1N1 Influenza Vaccine With or Without Adjuvant

Primary: Percentage of Subjects Age 6-11 Months Achieving Seroconversion or significant increase in Antibody Assayed by HAI Method Against A/California (H1N1) Strain After Intramuscular Inactivated, Split-virion A/H1N1 Influenza Vaccine With or Without Adjuvant

Primary: Percentage of Subjects Age 6-11 Months Achieving Seroconversion or significant increase in Antibody Assayed by HAI Method Against A/California (H1N1) Strain After Intramuscular Inactivated, Split-virion A/H1N1 Influenza Vaccine With or Without Adjuvant

Primary: Percentage of Subjects Age 12-35 Months Achieving Seroconversion or significant increase in Antibody Assayed by HAI Method Against A/California (H1N1) Strain After Intramuscular Inactivated, Split-virion A/H1N1 Influenza Vaccine With or Without Adjuvant

Primary: Percentage of Subjects Age 12-35 Months Achieving Seroconversion or significant increase in Antibody Assayed by HAI Method Against A/California (H1N1) Strain After Intramuscular Inactivated, Split-virion A/H1N1 Influenza Vaccine With or Without Adjuvant

Primary: Percentage of Subjects Age 6 to 11 Months with Neutralizing Antibody Titers ≥40 (1/dil) Assayed by Seroneutralization Method Against A/California (H1N1) Strain After Intramuscular Inactivated, Split-virion A/H1N1 Influenza Vaccine With or Without Adjuvant

Primary: Percentage of Subjects Age 6 to 11 Months with Neutralizing Antibody Titers ≥40 (1/dil) Assayed by Seroneutralization Method Against A/California (H1N1) Strain After Intramuscular Inactivated, Split-virion A/H1N1 Influenza Vaccine With or Without Adjuvant

Primary: Percentage of Subjects Age 12-35 Months with Neutralizing Antibody Titers ≥ 40 (1/dil) Assayed by Seroneutralization Method Against A/California (H1N1) Strain After Intramuscular Inactivated, Split-virion A/H1N1 Influenza Vaccine With or Without Adjuvant

Primary: Percentage of Subjects Age 12-35 Months with Neutralizing Antibody Titers ≥ 40 (1/dil) Assayed by Seroneutralization Method Against A/California (H1N1) Strain After Intramuscular Inactivated, Split-virion A/H1N1 Influenza Vaccine With or Without Adjuvant

Primary: Geometric Mean Titers (GMTs) of Neutralizing Antibody Assayed by Seroneutralization Method Against A/California (H1N1) Strain in Subjects Age 6-11 Months After Intramuscular Inactivated, Split-virion A/H1N1 Influenza Vaccine With or Without Adjuvant

Primary: Geometric Mean Titers (GMTs) of Neutralizing Antibody Assayed by Seroneutralization Method Against A/California (H1N1) Strain in Subjects Age 6-11 Months After Intramuscular Inactivated, Split-virion A/H1N1 Influenza Vaccine With or Without Adjuvant

Primary: Geometric Mean Titers (GMTs) of Neutralizing Antibody Assayed by Seroneutralization Method Against A/California (H1N1) Strain in Subjects Age 12-35 Months After Intramuscular Inactivated, Split-virion A/H1N1 Influenza Vaccine With or Without Adjuvant

Primary: Geometric Mean Titers (GMTs) of Neutralizing Antibody Assayed by Seroneutralization Method Against A/California (H1N1) Strain in Subjects Age 12-35 Months After Intramuscular Inactivated, Split-virion A/H1N1 Influenza Vaccine With or Without Adjuvant

Primary: Percentage of Subjects Age 6-11 Months with 2- and 4-fold Increase in Neutralizing Antibody Titers Assayed by Seroneutralization Against A/California (H1N1) Strain After Inactivated, Split-virion A/H1N1 Influenza Vaccine With or Without Adjuvant

Primary: Percentage of Subjects Age 6-11 Months with 2- and 4-fold Increase in Neutralizing Antibody Titers Assayed by Seroneutralization Against A/California (H1N1) Strain After Inactivated, Split-virion A/H1N1 Influenza Vaccine With or Without Adjuvant

Primary: Percentage of Subjects Age 12-35 Months with 2- and 4-fold Increase in Neutralizing Antibody Titers Assayed by Seroneutralization Against A/California (H1N1) Strain After Inactivated, Split-virion A/H1N1 Influenza Vaccine With or Without Adjuvant

Primary: Percentage of Subjects Age 12-35 Months with 2- and 4-fold Increase in Neutralizing Antibody Titers Assayed by Seroneutralization Against A/California (H1N1) Strain After Inactivated, Split-virion A/H1N1 Influenza Vaccine With or Without Adjuvant

Primary: Geometric Mean Titers (GMTs) of Antibody Assayed by SRH Method Against A/California (H1N1) Strain in Subjects Age 6 to 11 Months Old Before and After Vaccination with Inactivated, Split Virion Swine-origin A/H1N1 Influenza Vaccine With or Without Adjuvant

Primary: Geometric Mean Titers (GMTs) of Antibody Assayed by SRH Method Against A/California (H1N1) Strain in Subjects Age 6 to 11 Months Old Before and After Vaccination with Inactivated, Split Virion Swine-origin A/H1N1 Influenza Vaccine With or Without Adjuvant

Primary: Geometric Mean Titers of Antibody Assayed by SRH Against A/California (H1N1) Strain in Subjects Age 12-35 Months Before and After Vaccination with Intramuscular Inactivated, Split Virion Swine-origin A/H1N1 Influenza Vaccine With or Without Adjuvant

Primary: Geometric Mean Titers of Antibody Assayed by SRH Against A/California (H1N1) Strain in Subjects Age 12-35 Months Before and After Vaccination with Intramuscular Inactivated, Split Virion Swine-origin A/H1N1 Influenza Vaccine With or Without Adjuvant

Primary: Percentage of Subjects Age 6 to 11 Months Old With Seroprotection Against A/California (H1N1) Strain Following Vaccination with Intramuscular Inactivated, Split Virion Swine-origin A/H1N1 Influenza Vaccine With or Without Adjuvant

Primary: Percentage of Subjects Age 6 to 11 Months Old With Seroprotection Against A/California (H1N1) Strain Following Vaccination with Intramuscular Inactivated, Split Virion Swine-origin A/H1N1 Influenza Vaccine With or Without Adjuvant

Primary: Percentage of Subjects Age 12 to 35 Months Old With Seroprotection Against A/California (H1N1) Strain Following Vaccination with Intramuscular Inactivated, Split Virion Swine-origin A/H1N1 Influenza Vaccine With or Without Adjuvant

Primary: Percentage of Subjects Age 12 to 35 Months Old With Seroprotection Against A/California (H1N1) Strain Following Vaccination with Intramuscular Inactivated, Split Virion Swine-origin A/H1N1 Influenza Vaccine With or Without Adjuvant

Primary: Percentage of Subjects Age 12 to 35 Months Old Reporting Solicited Injection-site or Systemic Reactions After Any Vaccination with Intramuscular Inactivated, Split Virion Swine-origin A/H1N1 Influenza Vaccine With or Without Adjuvant

Primary: Percentage of Subjects Age 12 to 35 Months Old Reporting Solicited Injection-site or Systemic Reactions After Any Vaccination with Intramuscular Inactivated, Split Virion Swine-origin A/H1N1 Influenza Vaccine With or Without Adjuvant

Primary: Percentage of Subjects Age 6 to 11 Months Old Reporting Solicited Injection-site or Systemic Reactions After Any Vaccination with Intramuscular Inactivated, Split Virion Swine-origin A/H1N1 Influenza Vaccine With or Without Adjuvant

Primary: Percentage of Subjects Age 6 to 11 Months Old Reporting Solicited Injection-site or Systemic Reactions After Any Vaccination with Intramuscular Inactivated, Split Virion Swine-origin A/H1N1 Influenza Vaccine With or Without Adjuvant

Primary: Percentage of Subjects Age 24-35 Months with at Least One Solicited Reaction Listed in the EMA Note for Guidance Within 3 Days After Any and Each Vaccination with Intramuscular Inactivated, Split Virion A/H1N1 Influenza Vaccine With or Without Adjuvant

Primary: Percentage of Subjects Age 24-35 Months with at Least One Solicited Reaction Listed in the EMA Note for Guidance Within 3 Days After Any and Each Vaccination with Intramuscular Inactivated, Split Virion A/H1N1 Influenza Vaccine With or Without Adjuvant

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
Immunogenicity and Safety of Multiple Formulations of an Intramuscular Inactivated, Split Virion Swine-origin A/H1N1 Influenza Vaccine With and Without Adjuvant in Healthy European Subjects Aged 6 to 35 Months